title: The endocannabinoid system is modulated in response to spinal cord injury in rats.
abstract: Endocannabinoids are lipid mediators with protective effects in many diseases of the nervous system. We have studied the modulation of the endocannabinoid system after a spinal cord contusion in rats. In early stages, lesion induced increases of anandamide and palmitoylethanolamide (PEA) levels, an upregulation of the synthesizing enzyme NAPE-phospholipase D and a downregulation of the degradative enzyme FAAH. In delayed stages, lesion induced increases in 2-arachidonoylglycerol and a strong upregulation of the synthesizing enzyme DAGL-alpha, that is expressed by neurons, astrocytes and immune infiltrates. The degradative enzyme MAGL was also moderately increased but only 7 days after the lesion. We have studied the cellular targets for the newly formed endocannabinoids using RT-PCR and immunohistochemistry against CB(1) and CB(2) receptors. We observed that CB(1) was constitutively expressed by neurons and oligodendrocytes and induced in reactive astrocytes. CB(2) receptor was strongly upregulated after lesion, and mostly expressed by immune infiltrates and astrocytes. The endocannabinoid system may represent an interesting target for new therapeutical approaches to spinal cord injury.
authors.affiliation: Laboratorio de Neuroinflamacion, Unidad de Neurología Experimental (Research Unit associated to the Instituto Cajal, CSIC, Madrid), Hospital Nacional de Paraplejicos, Toledo, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Garcia-Ovejero
authors.forename: Angel
authors.initials: A
authors.lastname: Arevalo-Martin
authors.forename: Stefania
authors.initials: S
authors.lastname: Petrosino
authors.forename: Fabian
authors.initials: F
authors.lastname: Docagne
authors.forename: Carlos
authors.initials: C
authors.lastname: Hagen
authors.forename: Tiziana
authors.initials: T
authors.lastname: Bisogno
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.forename: Carmen
authors.initials: C
authors.lastname: Guaza
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Marzo
authors.forename: Eduardo
authors.initials: E
authors.lastname: Molina-Holgado
mesh_terms: D000577:Amides; D000581:Amidohydrolases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D063388:Endocannabinoids; D004983:Ethanolamines; D005989:Glycerides / Q000378:metabolism; D007150:Immunohistochemistry; D008071:Lipoprotein Lipase / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000378:metabolism; D010169:Palmitic Acids / Q000378:metabolism; D010739:Phospholipase D / Q000235:genetics / Q000378:metabolism; D053284:Polyunsaturated Alkamides / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000378:metabolism*; D013119:Spinal Cord Injuries / Q000201:enzymology / Q000378:metabolism*; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000577:Amides; D000581:Amidohydrolases; D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D004983:Ethanolamines; D005989:Glycerides; D008071:Lipoprotein Lipase; D010169:Palmitic Acids; D010739:Phospholipase D; D053284:Polyunsaturated Alkamides; D012333:RNA, Messenger; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D000099252:Fatty Acid Amide Hydrolases; C469526:Cnr2 protein, rat; C005958:palmidrol; C094503:glyceryl 2-arachidonate; C527163:Napepld protein, rat; C078814:anandamide